Piperidine → HCID 60164409, compound

HRID 1398714Notes

Reaction equation

HRID 1398714 reaction equation
Br[C:2]1[C:3]([F:18])=[CH:4][C:5]2[N:9]=[CH:8][N:7]([C:10]3[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[N:11]=3)[C:6]=2[CH:17]=1.N1CCCCC1.[S:25]1[CH:29]=[CH:28][N:27]=[C:26]1[C:30]([OH:34])([C:32]#[CH:33])[CH3:31]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[NH2:16][C:12]1[N:11]=[C:10]([N:7]2[C:6]3[CH:17]=[C:2]([C:33]#[C:32][C:30]([C:26]4[S:25][CH:29]=[CH:28][N:27]=4)([OH:34])[CH3:31])[C:3]([F:18])=[CH:4][C:5]=3[N:9]=[CH:8]2)[CH:15]=[CH:14][N:13]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 582215512-(Thiazol-2-yl)but-3-yn-2-olHCID 68181830HCID 68181830, compound

Product 1

HCID 60164409HCID 60164409, compoundYield 17.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
75 °C

Procedure

To a pressure tube was added 4-(6-Bromo-5-fluoro-benzoimidazol-1-yl)-pyrimidin-2-ylamine (66%, 250 mg, 0.54 mmol), piperidine (1.5 mL), tetrakis(triphenylphosphine)palladium (61.9 mg, 0.05 mmol), copper(I) iodide (10.2 mg, 0.05 mmol) and 2-(1,3-thiazol-2-yl)but-3-yn-2-ol (164.09 mg, 1.07 mmol), degassed with N2 for 5 min and stirred at 75° C. for 3 hr before concentrating in vacuo. The crude product was purified by column chromatography (Biotage) eluted with DCM: methanol gradient (98:2 to 90:10). The product obtained was triturated with methanol to obtain the title compound as an off-white solid (35 mg, 17.1% yield). 1H NMR (500 MHz, DMSO) delta 1.94 (3H, s), 7.08 (1H, s), 7.13 (1H, d, J=5.36 Hz), 7.18 (2H, br. s.), 7.65-7.73 (2H, m), 7.78 (1H, d, J=3.15 Hz), 8.39 (1H, br. s.), 8.64 (1 H, d, J=6.46 Hz), 9.17 (1H, s); LC-MS: m/z+381.40 (M+H)+.

Workup

  1. customdegassed with N2 for 5 min
  2. concentrationbefore concentrating in vacuo
  3. customThe crude product was purified by column chromatography (Biotage)
  4. washeluted with DCM
  5. customThe product obtained
  6. customwas triturated with methanol

Sources & evidence

ORD record
ord-8a840ad367244c678ce91a94633c7552
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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